The
senescence
phenotype
is
heterogeneous,
as
observed
by
the
context-dependent
differential
expression
of
markers.
Here,
we
provide
evidence
to
demonstrate
an
inverse
relationship
in
pattern
two
murine
variants
p21
(p21v1,
and
p21v2)
aging
hemorrhagic
shock.
While
upregulation
p21v1
was
following
shock
injury,
p21v2
upregulated
aged
mouse.
We
further
show
that
response
is,
at
least,
partially
independent
p53.
Journal of Clinical Investigation,
Год журнала:
2024,
Номер
134(9)
Опубликована: Апрель 30, 2024
There
is
intense
interest
in
identifying
compounds
that
selectively
kill
senescent
cells,
termed
senolytics,
for
ameliorating
age-related
comorbidities.
However,
screening
senolytic
currently
relies
on
primary
cells
or
cell
lines
where
senescence
induced
vitro.
Given
the
complexity
of
across
tissues
and
diseases,
this
approach
may
not
target
develop
under
specific
conditions
vivo.
In
issue
JCI,
Lee
et
al.
describe
a
pipeline
high-throughput
drug
was
vivo
identify
HSP90
inhibitor
XL888
as
candidate
to
treat
idiopathic
pulmonary
fibrosis.
Abstract
Senescence
is
a
crucial
hallmark
of
ageing
and
significant
contributor
to
the
pathology
age-related
disorders.
As
committee
members
young
International
Cell
Association
(yICSA),
we
aim
synthesise
recent
advancements
in
identification,
characterisation,
therapeutic
targeting
senescence
for
clinical
translation.
We
explore
novel
molecular
techniques
that
have
enhanced
our
understanding
senescent
cell
heterogeneity
their
roles
tissue
regeneration
pathology.
Additionally,
delve
into
vivo
models
senescence,
both
non-mammalian
mammalian,
highlight
tools
available
advancing
contextual
senescence.
Furthermore,
discuss
innovative
diagnostic
senotherapeutic
approaches,
emphasising
potential
application.
Future
directions
research
are
explored,
underscoring
need
precise,
context-specific
classification
integration
advanced
technologies
such
as
machine
learning,
long-read
sequencing,
multifunctional
senoprobes
senolytics.
The
dual
role
promoting
homoeostasis
contributing
chronic
diseases
highlights
complexity
these
cells
improved
outcomes.
The
senescence
phenotype
is
heterogeneous,
as
observed
by
the
context-dependent
differential
expression
of
markers.
Here,
we
provide
evidence
to
demonstrate
an
inverse
relationship
in
pattern
two
murine
variants
p21
(p21v1,
and
p21v2)
aging
hemorrhagic
shock.
While
upregulation
p21v1
was
following
shock
injury,
p21v2
upregulated
aged
mouse.
We
further
show
that
response
is,
at
least,
partially
independent
p53.
